There are no medical treatments for promoting recovery from brain injury, only management of secondary effects such as bleeding or edema. Nevertheless, some recovery does occur with time but this process is poorly understood. Our recent work, indicating that recovery of locomotor ability after unilateral sensorimotor cortex injury can be accelerated or slowed by a single drug treatment combined with experience, has important implications. This effect may offer some insight into the processes of spontaneous recovery and provide a scientific basis to modernize the classic, but controversial hypothesis of diaschisis - a functional depression of brain areas remote from the lesion but contributing to symptoms. We will directly test the hypothesis that a functional depression occurs in intact areas after brain injury and produces behavioral symptoms. We will begin to determine the mechanisms producing the proposed functional depression by measuring, and attempting to manipulate, metabolic and neurochemical processes which we hypothesize result in the functional depression after brain injury. Behavioral testing, together with physiological measures, after cortical injury will be examined following drug and experience treatments. By these converging operations we may begin to establish causal relationships between symptoms and the hypothesized functional depression. We will study a model of stroke in rat to extend our findings to the most frequent cause of human brain damage. To determine if the treatment can promote recovery in a higher species and other brain injury-induced symptoms, we will study the loss of depth perception after visual cortex ablation in cats. The experiments use various lesion methods, behavioral tests, pharmacology, liquid chromatography, histochemistry, and autoradiography. These data will provide an understanding of some of the mechanisms influencing recovery from brain injury and should lead to a treatment for stroke patients.